Research Opportunities

• Graduate student may apply through the MCB Program and then should contact Dr. Fero regarding opportunities for 2nd year rotations or thesis projects. 
• Postdoctoral fellows, or clinical fellows should contact Dr. Fero directly. 
• Undergraduate students who have completed cousework in biology and chemistry may apply for undergraduate research projects through the UW Undergraduate Research Program. 
• Undergraduate students from outside institutions may apply for summer internships through the FHCRC summer undergraduate research program.

Choosing a Research Project
Crucial to the success of any research project is to choose a project that is significant, informative, and creative. It must also be feasible within your time frame and skill level. An important aspect of research training to perfect your skills at oral and written presentations of your work to a variety of audiences. It is also important to learn the ropes for competitive research funding.  The lab provide mentorship for all of these aspects of a research project. In addition, undergraduates and entry level technicians need to be paired up with graduate level researchers to help teach skills and oversee their daily progress.

Major Areas of Research
The Fero lab is engaged in research activities on a variety of interesting topics. Our work has been highly interactive and collaborative with other scientists at the Center, at the University of Washington, and around the world.

1. Control of normal cell growth by cell cycle inhibitors
Our lab has studied the cellular and physiological roles of cell cycle inhibitor proteins by studying mouse models with mutations of these genes. This includes the p27Kip1 (Cdkn1b) cdk inhibitor gene, and other inhibitors of the cyclin D pathway including p21, and Rb family members. Deletion of p27 in knockout mice has demonstrated that this protein ordinarily limits the overall size of adult animals as well as particular tissues including the thymus, spleen and intermediate lobe of the pituitary. Interestingly, p27 and other cell cycle inhibitors are also crucial for maintaining cellular quiescence in sensory tissues such as the cochlea and retina. We are interested in the role of these cell cycle inhibitors  in cancer, which is characterized by clonal hyper-proliferation.  On the flip-side we are also interested in the requirement of Cdk inhibitor proteins to maintain normal cellular quiescence and whether celluar regeneration can be augmented by removing their inhibitory activity. This included colloborative efforts with the Roberts, Clurman, Kemp labs here at the Center and auditory specialists at the University of Washington and across the globe.  Key findings of this work has included:

•         The p27 Cdk inhibitor controls overal growth of animals
•         p27 is a haploid-insufficient tumor suppressor gene in multiple tissues
•         Loss of p27 causes spontaneous pars intermedia pituitary tumors which are phenotypically distinct from those found in Rb knockouts
•         The continuous presence of p27 is necessary to maintain cellular quiescence in the auditory organ of Corti
•         The absence of p27 leads constitutive cyclin A/Cdk2 and cyclin D/Cdk4 activity in thymocytes and increases their susceptibility to growth factors.
•         Overall organ size in the thymus and spleen is constrained by p27 through a cell non-autonomous mechanism involving cyclin D/Cdk 4 in stromal tissues.

2. Lymphomagenesis by the Xpcl1 (miR-106a~363) miRNA cluster
Using a Maloney murine leukemia virus (M-MuLV) mutagenesis screen we demonstrated that p27 knockout mice have a high rate of T-cell lymphomagenesis. In collaboration with scientists in the Clurman laboratory, here a the Center, we identified Myc, as cooperating oncogenes, as well as a novel non-coding gene called Xpcl1. Following our initial discovery of Xpcl1 (X-chromosomal p27 cooperating locus) the gene has been shown to encode a highly conserved cluster of microRNAs, termed miR-106a~363. In recent work we have shown that Xpcl1 is a potent oncogene in T-cell lymphomas. MicroRNAs from the Xpcl1 cluster target CD69 during normal and regulate the distribution of T-cell subsets during thymopoiesis.  It also up-regulates p27 by activating the FoxO family of transcription factors, and thereby exhibits mixed oncogenic and anti-oncogenic effects. Deletion of p27 cooperates with miR-106a~363 overexpression in T-cell lymphomagenesis by overcoming this tumor suppressor activity.

3. Cell fate determination during megakaryopoiesis
In order to control cell growth in useful ways it is important to be able to influence, not just cell growth, but also the differentiation and cell fate determinations that accompanies normal cellular growth.  We are using the megakaryocyte-erythroid progenitor (MEP) cell as a model of this cell fate determination step in an effort to improve our understanding and ability of growing megakaryocytes and platelets in culture. A major challenge of these bipotent hematopoietic cells is the task of prospectively identifying this rare cell population from admixed bone marrow cells. Although a variety of antibody markers are available at best we can only partially purify MEPs from whole bone marrow.  Our lab is characterizing the ability of intrinsic markers, i.e. endogenous promoters coupled to fluorescent proteins, to act as prospective markers of MEPs and other components of the megakaryocyte growth pathway. A major aspect of this work is to develop novel methods of interrogating the expression profiles of single cells using novel biochemical techniques coupled with 2nd generation RNASeq technology.  By determining the expression profile of individual cells in a complex mixture we may soon be able to determine the true heterogeneity of gene expression during all stages of hematopoietic cell growth or at any aspect of growth and differentiation.